The Protective Effects of Ketodiet in Salt‐Sensitive Hypertension

Abstract

Two‐thirds of hypertension cases in the United States are positively correlated with excessive weight gain. The ketogenic diet gained popularity through the weight loss community. It’s a low‐carb high‐fat diet triggering the body to burn fat for energy instead of carbohydrates. Dietary manipulation, ketoacid supplementation can potentially exert a cardiovascular protective effect in chronic renal failure. We hypothesized that ketodiet can have beneficial effects during the development of salt‐induced hypertension. The Dahl Salt Sensitive (SS) rats fed a high salt diet develop salt‐induced hypertension accompanied by kidney injury. To test effect of ketodiet, the Dahl SS rats were given either 4% NaCl diet (HS; Dyets Inc, 113756) or 4% NaCl modified ketodiet (KD; Harland Tekland, TD 190564) with free access to water for 4 weeks. Blood pressure was monitored with telemetry throughout the study, and urine samples were collected in metabolic cages on days 0, 7, 14, and 28. At the end of the protocol animals were sacrificed and blood and kidney tissues were harvested for following analyses. Urine and plasma samples were analyzed to estimate electrolyte and glucose homeostasis. Dahl SS rats fed a KD had a lower blood pressure compared to control rats fed a HS diet. By the end of the experiment mean arterial pressure was 143 ± 4 mmHg vs 156 ± 4 mmHg for Dahl SS rats fed a KD and HS diets, respectively (p<0.05). The KD group has gained less weight (70 ± 8 vs 85 ± 12 g, p<0.05 compared to HS). Furthermore, we observed reduced renal hypertrophy with decreased kidney to body weight ratio (0.94 ± 0.05 vs 1.14 ± 0.06 p<0.05 compared to HS) and smaller kidneys (3.0 ± 0.1 vs 4.0 ± 0.3 g, p<0.05 compared to HS) in the KD animals. The rats on KD experienced hypoglycemia (305 ± 8 vs 364 ± 11 mg/dL, p<0.05 compared to HS) although they had comparably the same as the HS group amount of food consumption (17 ± 2 vs 19 ± 2 g/day, p>0.05). Metabolic cage studies revealed diminished diuresis (0.010 ± 0.001 ml/100g/h vs 0.020 ± 0.002 ml/100g/hr, p<0.05) in KD compared to HS group with no significant changes in electrolyte excretion. Glucose excretion has been reduced in a KD group (1.2 ± 0.5 vs 12.8 ± 4.8, glucose to creatinine ratio, p<0.05 compared to HS). Therefore, we can conclude that prolonged KD provide protective effect on the development of hypertension during HS challenge. Our data revealed that KD during HS challenge resulted in decreased blood pressure, reduced kidney hypertrophy and diminished levels of plasma glucose.